Genetics

The 12-kb GLA gene encoding α-galactosidase A is located on the X chromosome.1 Over 1000 GLA gene mutations have been identified.2 Fabry disease is an inherited disorder and most affected families have ‘private’ or unique mutations.1

Males with classical Fabry disease generally have no detectable α-galactosidase A activity. These individuals harbour a variety of GLA gene mutations, including rearrangements, splicing defects, missense or nonsense mutations, and complex mutations. In contrast, only missense mutations have been found in atypical variants, who usually have low or residual α-galactosidase A activity.3

Fabry disease is transmitted as an X-linked trait.1 Consequently, affected fathers pass the defective gene to all their daughters but never transmit the disease to their sons. Children conceived by heterozygous females have a 1 in 2 chance of inheriting the mutant gene. Sons who inherit the mutant gene from their mother will have the disease, while daughters will be heterozygotes who may develop clinical manifestations or may be asymptomatic.1

X-linked inheritance pattern of Fabry disease

References

  1. 1.Germain DP. (2010) Fabry disease. Orphanet J Rare Dis 5: 30.
  2. 2.Malte Lenders, Franciska Stappers, Eva Brand (2020); In Vitro and In Vivo Amenability to Migalastat in Fabry Disease, Mol Ther Methods Clin Dev. 2020 Dec 11; 19: 24–34.
  1. 3.Desnick RJ, Ioannou YA, Eng CM. α-Galactosidase A Deficiency: Fabry Disease. In: Valle D, Beaudet AL, Vogelstein B, Kinzler KW, Antonarakis SE, Ballabio A, et al., editors. The Online Metabolic and Molecular Bases of Inherited Disease. New York, NY: McGra